Mitochondrial dysfunction is a primary consequence of nearly all age-onset neurodegenerative diseases, and can be the consequence of exposure to even mild levels of a wide-range of environmental toxins. Surprisingly, the applicant's lab has uncovered that mitochondrial stress in one cell type can be communicated to a distal cell type that has not undergone mitochondrial stress. Using tissue specific promoters in the nematode C. elegans that drive expression of dsRNA of a subunit of complex IV of the ETC in the nervous system, it has been shown that neuronal mitochondrial stress can be communicated to distal cells, such as the intestine. The ability of the nervous system to communicate this mild stress results in increased longevity and survival of the entire animal. The goal of the proposed studies is to identify the source and nature of this signaling mechanism. PUBLIC HEALTH RELEVANCE: We have discovered that mitochondria from one cell can communicate to cells at a distance. This communication is initiated in the nervous system and ensures the survival of an animal under conditions of stress. The identity of the language in which these cells communicate will provide new avenues of therapy for people that suffer from diseases associated with mitochondrial malfunction, such as stroke, Alzheimer's, Parkinson's, Huntington's, diabetes and rare metabolic diseases.